Temporal and Regional Changes in IGF-1/IGF-1R Signaling in the Mouse Brain after Traumatic Brain Injury
- 1 January 2010
- journal article
- research article
- Published by Mary Ann Liebert Inc in Journal of Neurotrauma
- Vol. 27 (1), 95-107
- https://doi.org/10.1089/neu.2009.1002
Abstract
Although neurotrophic factors such as nerve growth factor, basic fibroblast growth factor, brain-derived neurotrophic factor, and neurotrophin 4/5 are elevated after traumatic brain injury (TBI), little is known about the endogenous response of insulin-like growth factor-1 (IGF-1). We evaluated IGF-1, IGF-1 receptor (IGF-1R), and total and phosphorylated Akt (p-Akt), a known downstream mediator of IGF-1 signaling, using ELISA, Western blotting, and immunohistochemistry at 1, 6, 24, 48, and 72 h following 0.5-mm controlled cortical impact brain injury in adult mice. IGF-1 was transiently upregulated in homogenates of injured cortex at 1 h, and cells with increased IGF-1 immunoreactivity were observed in and around the cortical contusion site up to 48 h. IGF-1R and total Akt levels in cortical homogenates were unchanged, although immunohistochemistry revealed regional changes. In contrast, serine p-Akt levels increased significantly in homogenates at 6 h post-injury. Interestingly, delayed increases in vascular IGF-1R, total Akt, and p-Akt immunostaining were observed in and around the cortical contusion. IGF-1 and its downstream mediators were also upregulated in the subcortical white matter. Our findings indicate that moderate TBI results in a brief induction of IGF-1 and its signaling components in the acute post-traumatic period. This may reflect an attempt at endogenous neuroprotection or repair.Keywords
This publication has 64 references indexed in Scilit:
- IGF-I gene delivery promotes corticospinal neuronal survival but not regeneration after adult CNS injuryExperimental Neurology, 2009
- Mild traumatic brain injury to the infant mouse causes robust white matter axonal degeneration which precedes apoptotic death of cortical and thalamic neuronsExperimental Neurology, 2008
- Insulin-like Growth Factor Type-I Receptor Internalization and Recycling Mediate the Sustained Phosphorylation of AktOnline Journal of Public Health Informatics, 2007
- Insulin‐like growth factor type 1 receptor signaling in the cells of oligodendrocyte lineage is required for normal in vivo oligodendrocyte development and myelinationGlia, 2006
- Increased Phosphorylation of Protein Kinase B and Related Substrates after Traumatic Brain Injury in Humans and RatsJournal of Cerebral Blood Flow & Metabolism, 2005
- Expression and changes of endogenous insulin-like growth factor-1 in neurons and glia in the gerbil hippocampus and dentate gyrus after ischemic insultNeurochemistry International, 2003
- Plasticity following Injury to the Adult Central Nervous System: Is Recapitulation of a Developmental State Worth Promoting?Journal of Neurotrauma, 2003
- Non-invasive intranasal insulin-like growth factor-I reduces infarct volume and improves neurologic function in rats following middle cerebral artery occlusionNeuroscience Letters, 2001
- A role for IGF-1 in the rescue of CNS neurons following hypoxic-ischemic injuryBiochemical and Biophysical Research Communications, 1992
- Differing expression of insulin‐like growth factor I in the developing and in the adult rat cerebellumActa Physiologica Scandinavica, 1988